Advertisement

Molecular Medicine

, Volume 14, Issue 1–2, pp 79–86 | Cite as

Nonviral Vector Gene Modification of Stem Cells for Myocardial Repair

  • Husnain K. Haider
  • Ibrahim Elmadbouh
  • Michel Jean-Baptiste
  • Muhammad Ashraf
Review Article

Abstract

Therapeutic angiogenesis and myogenesis restore perfusion of ischemic myocardium and improve left ventricular contractility. These therapeutic modalities must be considered as complementary rather than competing to exploit their advantages for optimal beneficial effects. The resistant nature of cardiomyocytes to gene transfection can be overcome by ex vivo delivery of therapeutic genes to the heart using genetically modified stem cells. This review article gives an overview of different vectors and delivery systems in general used for therapeutic gene delivery to the heart and provides a critical appreciation of the ex vivo gene delivery approach using genetically modified stem cells to achieve angiomyogenesis for the treatment of infarcted heart.

References

  1. 1.
    Lee MS, Lill M, Makkar RR (2004). Stem cell transplantation in myocardial infarction. Rev. Cardiovasc. Med. 5:82–98.PubMedGoogle Scholar
  2. 2.
    Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ (2003). Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289:194–202.CrossRefPubMedGoogle Scholar
  3. 3.
    Nordlie MA, Wold LE, Simkhovich BZ, Sesti C, Kloner RA (2006). Molecular aspects of ischemic heart disease: ischemia/reperfusion-induced genetic changes and potential applications of gene and RNA interference therapy. J. Cardiovasc. Pharmacol. Ther. 11:17–30.CrossRefPubMedGoogle Scholar
  4. 4.
    Dib N, et al. (2005). Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant. 14:11–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Smits PC (2004). Myocardial repair with autologous skeletal myoblasts: a review of the clinical studies and problems. Minerva Cardioangiol. 52:525–35.PubMedGoogle Scholar
  6. 6.
    Stamm C, et al. (2007). Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J. Thorac. Cardiovasc. Surg. 133:717–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Assmus B, et al. (2006). Transcoronary transplantation of progenitor cells after myocardial infarction. N. Engl. J. Med. 355:1222–32.CrossRefPubMedGoogle Scholar
  8. 8.
    Haider H, et al. (2004). Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. J. Mol. Med. 82:539–49.CrossRefPubMedGoogle Scholar
  9. 9.
    Yau TM, Kim C, Ng D, Li G, Zhang Y, Weisel RD, Li RK (2005). Increasing transplanted cell survival with cell-based angiogenic gene therapy. Ann. Thorac. Surg. 80:1779–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Ye L, Haider H, Jiang S, Ling LH, Ge R, Law PK, Sim EK (2005). Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model. Eur. J. Heart Fail. 7:945–52.CrossRefPubMedGoogle Scholar
  11. 11.
    Yla-Herttuala S, Martin JF (2000). Cardiovascular gene therapy. Lancet 355:213–22.CrossRefPubMedGoogle Scholar
  12. 12.
    Nabel EG (1995). Gene therapy for cardiovascular disease. Circulation 91:541–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Ye L, et al. (2007). Angiopoietin-1 for myocardial angiogenesis: a comparison between delivery strategies. Eur. J. Heart Fail. 9:458–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat. Med. 9:1195–201.CrossRefPubMedGoogle Scholar
  15. 15.
    Wang Y, Haider HK, Ahmad N, Xu M, Ge R, Ashraf M (2006). Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair. J. Mol. Cell Cardiol. 40:736–45.CrossRefPubMedGoogle Scholar
  16. 16.
    Jiang S, Haider H, Idris NM, Salim A, Ashraf M (2006). Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ. Res. 99:776–84.CrossRefPubMedGoogle Scholar
  17. 17.
    Clark PR, Hersh EM (1999). Cationic lipid-mediated gene transfer: current concepts. Curr. Opin. Mol. Ther. 1:158–76.PubMedGoogle Scholar
  18. 18.
    Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW (1999). Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery. Gene Ther. 6:643–50.CrossRefPubMedGoogle Scholar
  19. 19.
    da Cruz MT, Simoes S, Pires PP, Nir S, de Lima MC (2001). Kinetic analysis of the initial steps involved in lipoplex-cell interactions: effect of various factors that influence transfection activity. Biochim. Biophys. Acta 1510:136–51.CrossRefPubMedGoogle Scholar
  20. 20.
    Kircheis R, Wightman L, Wagner E (2001). Design and gene delivery activity of modified polyethylenimines. Adv. Drug Deliv. Rev. 53:341–58.CrossRefPubMedGoogle Scholar
  21. 21.
    Elmadbouh I, et al. (2004). Optimization of in vitro vascular cell transfection with non-viral vectors for in vivo applications. J. Gene Med. 6:1112–24.CrossRefPubMedGoogle Scholar
  22. 22.
    Mehier-Humbert S, Bettinger T, Yan F, Guy RH (2005). Plasma membrane poration induced by ultrasound exposure: implication for drug delivery. J. Control. Release 104:213–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Andre F, Mir IM (2004). DNA electrotransfer: its principles and an updated review of its therapeutic applications. Gene Ther. 11(Suppl 1):S33–42.CrossRefPubMedGoogle Scholar
  24. 24.
    Lawrie A, et al. (1999). Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro. Circulation 99:2617–20.CrossRefPubMedGoogle Scholar
  25. 25.
    Kondo I, et al. (2004). Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer: the first demonstration of myocardial transfer of a “functional” gene using ultrasonic microbubble destruction. J. Am. Coll. Cardiol. 44:644–53.CrossRefPubMedGoogle Scholar
  26. 26.
    Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC, Newman CM (2000). Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther. 7:2023–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Zhigang W, et al. (2004). Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats. Clin. Imaging 28:395–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Ohki S, Duax J (1986). Effects of cations and polyamines on the aggregation and fusion of phosphatidylserine membranes. Biochim. Biophys. Acta 861:177–86.CrossRefPubMedGoogle Scholar
  29. 29.
    Binder H, Arnold K, Ulrich AS, Zschornig O (2001). Interaction of Zn2+ with phospholipid membranes. Biophys. Chem. 90:57–74.CrossRefPubMedGoogle Scholar
  30. 30.
    Haberland A, Knaus T, Zaitsev SV, Stahn R, Mistry AR, Coutelle C, Haller H (1999). Calcium ions as efficient cofactor of polycation-mediated gene transfer. Biochim. Biophys. Acta 1445:21–30.CrossRefPubMedGoogle Scholar
  31. 31.
    Pichon C, Guerin B, Refregiers M, Goncalves C, Vigny P, Midoux P (2002). Zinc improves gene transfer mediated by DNA/cationic polymer complexes. J. Gene Med. 4:548–59.CrossRefPubMedGoogle Scholar
  32. 32.
    Fuchs O, Babusiak M, Vyoral D, Petrak J (2003). Role of zinc in eukaryotic cells, zinc transporters and zinc-containing proteins. Sb. Lek. 104:157–70.PubMedGoogle Scholar
  33. 33.
    Felgner PL, et al. (1997). Nomenclature for synthetic gene delivery systems. Hum. Gene Ther. 8:511–2.CrossRefPubMedGoogle Scholar
  34. 34.
    Goncalves C, Pichon C, Guerin B, Midoux P (2002). Intracellular processing and stability of DNA complexed with histidylated polylysine conjugates. J. Gene Med. 4:271–81.CrossRefPubMedGoogle Scholar
  35. 35.
    Pichon C, Goncalves C, Midoux P (2001). Histidinerich peptides and polymers for nucleic acids delivery. Adv. Drug Deliv. Rev. 53:75–94.CrossRefPubMedGoogle Scholar
  36. 36.
    Breunig M, Lungwitz U, Liebl R, Fontanari C, Klar J, Kurtz A, Blunk T, Goepferich A (2005). Gene delivery with low molecular weight linear polyethylenimines. J. Gene Med. 7:1287–98.CrossRefPubMedGoogle Scholar
  37. 37.
    Simoes S, Filipe A, Faneca H, Mano M, Penacho N, Duzgunes N, de Lima MP (2005). Cationic liposomes for gene delivery. Expert Opin. Drug Deliv. 2:237–54.CrossRefPubMedGoogle Scholar
  38. 38.
    Karmali PP, Chaudhuri A (2007). Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open questions, and future promises. Med. Res. Rev. 27:696–722.CrossRefPubMedGoogle Scholar
  39. 39.
    Maitani Y, Igarashi S, Sato M, Hattori Y (2007). Cationic liposome (DC-Chol/DOPE = 1:2) and a modified ethanol injection method to prepare liposomes, increased gene expression. Int. J. Pharm. 342:33–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Boktov J, Hirsch-Lerner D, Barenholz Y (2007). Characterization of the interplay between the main factors contributing to lipoplex-mediated transfection in cell cultures. J. Gene Med. 99:884–93.CrossRefGoogle Scholar
  41. 41.
    Nguyen LT, Atobe K, Barichello JM, Ishida T, Kiwada H (2007). Complex formation with plasmid DNA increases the cytotoxicity of cationic liposomes. Biol. Pharm. Bull. 30:751–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Hebert E (2003). Improvement of exogenous DNA nuclear importation by nuclear localization signal-bearing vectors: a promising way for non-viral gene therapy? Biol. Cell. 95:59–68.CrossRefPubMedGoogle Scholar
  43. 43.
    Luton D, et al. (2004). Gene transfection into fetal sheep airways in utero using guanidinium-cholesterol cationic lipids. J. Gene Med. 6:328–36.CrossRefPubMedGoogle Scholar
  44. 44.
    Tranchant I, Thompson B, Nicolazzi C, Mignet N, Scherman D (2004). Physicochemical optimisation of plasmid delivery by cationic lipids. J. Gene Med. 6(Suppl 1):S24–35.CrossRefPubMedGoogle Scholar
  45. 45.
    Faneca H, Simoes S, de Lima MC (2002). Evaluation of lipid-based reagents to mediate intracellular gene delivery. Biochim. Biophys. Acta 1567:23–33.CrossRefPubMedGoogle Scholar
  46. 46.
    Simonson OE, Svahn MG, Tornquist E, Lundin KE, Smith CI (2005). Bioplex technology: novel synthetic gene delivery pharmaceutical based on peptides anchored to nucleic acids. Curr. Pharm. Des. 11:3671–80.CrossRefPubMedGoogle Scholar
  47. 47.
    Wiehe JM, et al. (2006). Efficient transient genetic labeling of human CD34+ progenitor cells for in vivo application. Regen. Med. 1:223–34.CrossRefPubMedGoogle Scholar
  48. 48.
    Jacobsen F, et al. (2006). Nucleofection: a new method for cutaneous gene transfer? J. Biomed. Biotechnol. 2006:26060.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hoshino K, et al. (2006). Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres. Gene Ther. 13:1320–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Jo J, Nagaya N, Miyahara Y, Kataoka M, Harada-Shiba M, Kangawa K, Tabata Y (2007). Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction: benefit of a novel nonviral vector, cationized dextran. Tissue Eng. 13:313–22.CrossRefPubMedGoogle Scholar
  51. 51.
    Ye L, Haider H, Jiang S, Tan RS, Ge R, Law PK, Sim EK (2007). Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165 and angiopoietin-1. Eur. J. Heart Fail. 9:15–22.CrossRefPubMedGoogle Scholar
  52. 52.
    Yau TM, Li G, Weisel RD, Reheman A, Jia ZQ, Mickle DA, Li RK (2004). Vascular endothelial growth factor transgene expression in cell-transplanted hearts. J. Thorac. Cardiovasc. Surg. 127:1180–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Askari AT, et al. (2003). Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362:697–703.CrossRefPubMedGoogle Scholar
  54. 54.
    Zhang M, et al. (2007). SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J. 21:3197–207.CrossRefPubMedGoogle Scholar
  55. 55.
    Elmadbouh I, Haider H, Jiang S, Idris NM, Lu G, Ashraf M (2007). Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J. Mol. Cell Cardiol. 42:792–803.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Elmadbouh I, Chen Y, Louedec L, Silberman S, Pouzet B, Meilhac O, Michel JB. (2005). Mesothelial cell transplantation in the infarct scar induces neovascularization and improves heart function. Cardiovasc. Res. 68:307–17.CrossRefPubMedGoogle Scholar
  57. 57.
    Saeki Y, Matsumoto N, Nakano Y, Mori M, Awai K, Kaneda Y (1997). Development and characterization of cationic liposomes conjugated with HVJ (Sendai virus): reciprocal effect of cationic lipid for in vitro and in vivo gene transfer. Hum. Gene Ther. 8:2133–41.CrossRefPubMedGoogle Scholar
  58. 58.
    Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, Yacoub MH (2001). Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation 104:I207–12.CrossRefPubMedGoogle Scholar
  59. 59.
    Miyamoto MI, et al. (2000). Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc. Natl. Acad. Sci. U. S. A. 97:793–8.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Huq F, Lebeche D, Iyer V, Liao R, Hajjar RJ (2004). Gene transfer of parvalbumin improves diastolic dysfunction in senescent myocytes. Circulation 109: 2780–5.CrossRefPubMedGoogle Scholar
  61. 61.
    Etzion S, et al. (2002). Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo: an unlimited source of cells for myocardial repair. Circulation 106:I125–30.PubMedGoogle Scholar
  62. 62.
    Murry CE, Kay MA, Bartosek T, Hauschka SD, Schwartz SM (1996). Muscle differentiation during repair of myocardial necrosis in rats via gene transfer with MyoD. J. Clin. Invest. 98:2209–17.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Pleger ST, et al. (2005). S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction. Mol. Ther. 12:1120–9.CrossRefPubMedGoogle Scholar
  64. 64.
    Sayeed-Shah U, et al. (1998). Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization. J. Thorac. Cardiovasc. Surg. 116:763–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Rosengart TK, et al. (1999). Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 100:468–74.CrossRefPubMedGoogle Scholar
  66. 66.
    Losordo DW, Dimmeler S (2004). Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation 109:2692–7.CrossRefPubMedGoogle Scholar
  67. 67.
    Tse HF, Lau CP (2007). Therapeutic angiogenesis with bone marrow-derived stem cells. J. Cardiovasc. Pharmacol. Ther. 12:89–97.CrossRefPubMedGoogle Scholar
  68. 68.
    Matsumoto R, et al. (2005). Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 25:1168–73.CrossRefPubMedGoogle Scholar
  69. 69.
    Tang GP, Yang Z, Zhou J (2006). Poly (ethylenimine)-grafted-poly [(aspartic acid)-co-lysine], a potential non-viral vector for DNA delivery. J. Biomater. Sci. Polym. Ed. 17:461–80.CrossRefPubMedGoogle Scholar
  70. 70.
    Hattan N, Warltier D, Gu W, Kolz C, Chilian WM, Weihrauch D (2004). Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth. Am. J. Physiol. Heart Circ. Physiol. 287:H488–93.CrossRefPubMedGoogle Scholar
  71. 71.
    Ye L, et al. (2007). Transplantation of nanoparticle transfected skeletal myoblasts overexpressing vascular endothelial growth factor-165 for cardiac repair. Circulation 116:I113–20.CrossRefPubMedGoogle Scholar
  72. 72.
    Laitinen M, et al. (2000). Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty. Hum. Gene Ther. 11:263–70.CrossRefPubMedGoogle Scholar
  73. 73.
    Hedman M, et al. (2003). Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107:2677–83.CrossRefPubMedGoogle Scholar
  74. 74.
    Kutryk MJ, et al. (2002). Local intracoronary administration of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis: results of the randomized investigation by the Thoraxcenter of antisense DNA using local delivery and IVUS after coronary stenting (ITALICS) trial. J. Am. Coll. Cardiol. 39:281–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Symes JF, Losordo DW, Vale PR, Lathi KG, Esakof DD, Mayskiy M, Isner JM (1999). Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann. Thorac. Surg. 68:830–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Sarkar N, et al. (2001). Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease: 12-month follow-up: angiogenic gene therapy. J. Intern. Med. 250:373–81.CrossRefPubMedGoogle Scholar

Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Husnain K. Haider
    • 1
  • Ibrahim Elmadbouh
    • 1
    • 2
  • Michel Jean-Baptiste
    • 2
  • Muhammad Ashraf
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of CincinnatiCincinnatiUSA
  2. 2.INSERM Unit 698, Cardiovascular RemodelingCHU Xavier Bichat-Claude BernardParisFrance

Personalised recommendations